\ BIP! Finder for COVID-19 - Impact-based ranking

BIP! Finder for COVID-19

This version of BIP! Finder aims to ease the exploration of COVID-19-related literature by enabling ranking articles based on various impact metrics.

Last Update: 18 - 01 - 2023 (628506 entries)

Provided impact measures:
Popularity: Citation-based measure reflecting the current impact.
Influence: Citation-based measure reflecting the total impact.
Reader Attention: The current number of Mendeley readers.
Social Media Attention: The number of recent tweets related to this article.
*More details on these impact measures can be found here.
Score interpretations:
Exceptional score (in top 0.01%).
Substantial score (in top 1%).
Average score (in bottom 99%).
Score not available.
Main data sources:
CORD-19 dataset(1) (list of papers)
LitCovid hub(2) (list of papers)
PMC & PubMed (citations)
Mendeley (number of readers)
COVID-19-TweetIDs(3) (tweets)

Use:  Impact  Relevance & Impact
TitleVenueYearImpactSource
551Mental health status among family members of Healthcare workers in Ningbo, China, during the COVID-19 outbreak: a cross-sectional study  

BACKGROUND: To date, the psychological impact of COVID-19 epidemic among family members of health care workers (HCWs) in China has been neglected. This cross-sectional study investigates the mental health status and related factors in families of HCWs employed in designated hospitals in Ningbo, China. METHODS: Family members of HCWs in five designated hospitals in Ningbo, China, were recruited in February, 2020 for this study. Demographic variables, COVID-19-related events in the lives of the participants, knowledge of COVID-19, and the working status of family members (that is, HCWs) were collected using online self-administered questionnaires. Mental health status was assessed using the Chinese versions of the Generalized Anxiety Disorder-7 (GAD-7) and Patient Health Questionnaire-9 (PHQ-9). Multivariable logistic regression analyses were performed to identify the main factors associated with the mental health conditions. RESULTS: In total, 845 participants completed the questionnaires correctly (95.80% response rate). The prevalence of anxiety and depression symptoms were respectively 33.73% (95% CI: 30.53–36.92%) and 29.35% (95% CI: 26.27–32.43%) when a cut-off score of 5 was used for GAD-7 and PHQ-9. Risk factors for anxiety symptoms included more time (hours) spent thinking about the COVID-19, and whether or not family members (that is, HCWs) had direct contact with confirmed or suspected COVID-19 patients while high participants’ self-reported safety scores for HCW’s protective equipment was a protective factor. More time (hours) spent thinking about COVID-19, longer average working time per week worked by family members (that is, HCWs), and being parents and other next of kin of HCWs were risk factors for depressive symptoms. Compared to participants who were HCWs, participants who were private sector workers were more likely to develop depressive symptoms, while government or institutional employees were less likely to suffer from depressive symptoms. CONCLUSIONS: Psychological responses to COVID-19 have been dramatic among family members of HCWs during the rising phase of the outbreak. Our findings provide strong evidence to examine and attend to the mental health of this population during the COVID-19 epidemic.

BMC Psychiatry2020       LitCov and CORD-19
552COVID-19 and Racial/Ethnic Disparities  

N/A

JAMA2020       LitCov and CORD-19
553Practical nursing recommendations for palliative care for people with dementia living in long-term care facilities during the COVID-19 pandemic: A rapid scoping review  

BACKGROUND: The acute nature of COVID-19 and its effects on society in terms of social distancing and quarantine regulations affect the provision of palliative care for people with dementia who live in long-term care facilities. The current COVID-19 pandemic poses a challenge to nursing staff, who are in a key position to provide high-quality palliative care for people with dementia and their families. OBJECTIVE: To formulate practice recommendations for nursing staff with regard to providing palliative dementia care in times of COVID-19. DESIGN AND METHOD: A rapid scoping review following guidelines from the Joanna Briggs Institute. Eligible papers focused on COVID-19 in combination with palliative care for older people or people with dementia and informed practical nursing recommendations for long-term care facilities. After data extraction, we formulated recommendations covering essential domains in palliative care adapted from the National Consensus Project's Clinical Practice Guidelines for Quality Palliative Care. DATA SOURCES: We searched the bibliographic databases of PubMed, CINAHL and PsycINFO for academic publications. We searched for grey literature using the search engine Google. Moreover, we included relevant letters and editorials, guidelines, web articles and policy papers published by knowledge and professional institutes or associations in dementia and palliative care. RESULTS: In total, 23 documents (7 (special) articles in peer-reviewed journals, 6 guides, 4 letters to editors, 2 web articles (blogs), 2 reports, a correspondence paper and a position paper) were included. The highest number of papers informed recommendations under the domains ‘advance care planning’ and ‘psychological aspects of care’. The lowest number of papers informed the domains ‘ethical care’, ‘care of the dying’, ‘spiritual care’ and ‘bereavement care’. We found no papers that informed the ‘cultural aspects of care’ domain. CONCLUSION: Literature that focuses specifically on palliative care for people with dementia in long-term care facilities during the COVID-19 pandemic is still largely lacking. Particular challenges that need addressing involve care of the dying and the bereaved, and ethical, cultural and spiritual aspects of care. Moreover, we must acknowledge grief and moral distress among nursing staff. Nursing leadership is needed to safeguard the quality of care and nursing staff should work together within an interprofessional care team to initiate advance care planning conversations in a timely manner, to review and document advance care plans, and to adapt goals of care as they may change due to the COVID-19 situation. Tweetable abstract: The current COVID-19 pandemic affects people living with dementia, their families and their professional caregivers. This rapid scoping review searched for academic and grey literature to formulate practical recommendations for nursing staff working in long-term care facilities on how to provide palliative care for people with dementia in times of COVID-19. There is a particular need for grief and bereavement support and we must acknowledge grief and moral distress among nursing staff. This review exposes practice and knowledge gaps in the response to COVID-19 that reflect the longstanding neglect and weaknesses of palliative care in the long-term care sector. Nursing leadership is needed to safeguard the quality of palliative care, interprofessional collaboration and peer support among nursing staff.

Int J Nurs Stud2020       LitCov and CORD-19
554Completion of the sequence of the genome of the coronavirus avian infectious bronchitis virus  

N/A

J Gen Virol1987       CORD-19
555International Society for Gynecologic Endoscopy (ISGE) guidelines and recommendations on gynecological endoscopy during the evolutionary phases of the SARS-CoV-2 pandemic  

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has raised some important interrogations on minimally invasive gynaecological surgery. The International Society of gynaecological Endoscopists (ISGE) has taken upon itself the task of providing guidance and best practice policies for all practicing gynaecological endoscopists. Factors affecting decision making processes in minimal invasive surgery (MIS) vary depending on factors such as the phase of the pandemic, policies on control and prevention, expertise and existing infrastructure. Our responsibility remains ensuring the safety of all health care providers, ancillary staff and patients during this unusual period. We reviewed the current literature related to gynecological and endoscopic surgery during the Coronavirus Disease 19 (COVID-19) crisis. Regarding elective surgery, universal testing for SARS-CoV-2 infection should be carried out wherever possible 40 h prior to surgery. In case of confirmed positive case of SARS-CoV-2, surgery should be delayed. Priority should be given to relatively urgent cases such as malignancies. ISGE supports medical optimization and delaying surgery for benign non-life-threatening surgeries. When possible, we recommend to perform cases by laparoscopy and to allow early discharges. Any procedure with risk of bowel involvement should be performed by open surgery as studies have found a high amount of viral RNA (ribonucleic acid) in stool. Regarding urgent surgery, each unit should create a risk assessment flow chart based on capacity. Patients should be screened for symptoms and symptomatic patients must be tested. In the event that a confirmed case of SARS-CoV-2 is found, every attempt should be made to optimize medical management and defer surgery until the patient has recovered and only emergency or life-threatening surgery should be performed in these cases. We recommend to avoid intubation and ventilation in SARS-CoV-2 positive patients and if at all possible local or regional anesthesia should be utilized. Patients who screen or test negative may have general anesthesia and laparoscopic surgery while strict protocols of infection control are upheld. Surgery in screen-positive as well as SARS-CoV-2 positive patients that cannot be safely postponed should be undertaken with full PPE with ensuring that only essential personnel are exposed. If available, negative pressure theatres should be used for patients who are positive or screen high risk. During open and vaginal procedures, suction can be used to minimize droplet and bioaerosol spread. In a patient who screens low risk or tests negative, although carrier and false negatives cannot be excluded, laparoscopy should be strongly considered. We recommend, during minimal access surgeries, to use strategies to reduce production of bioaerosols (such as minimal use of energy, experienced surgeon), to reduce leakage of smoke aerosols (for example, minimizing the number of ports used and size of incisions, as well as reducing the operating pressures) and to promote safe elimination of smoke during surgery and during the ports’ closure (such as using gas filters and smoke evacuation systems). During the post-peak period of pandemic, debriefing and mental health screening for staff is recommended. Psychological support should be provided as needed. In conclusion, based on the existent evidence, ISGE largely supports the current international trends favoring laparoscopy over laparotomy on a case by case risk evaluation basis, recognizing the different levels of skill and access to minimally invasive procedures across various countries.

Eur J Obstet Gynecol Reprod Bi2020       LitCov and CORD-19
556Origins of major human infectious diseases  

Many of the major human infectious diseases, including some now confined to humans and absent from animals, are ‘new’ ones that arose only after the origins of agriculture. Where did they come from? Why are they overwhelmingly of Old World origins? Here we show that answers to these questions are different for tropical and temperate diseases; for instance, in the relative importance of domestic animals and wild primates as sources. We identify five intermediate stages through which a pathogen exclusively infecting animals may become transformed into a pathogen exclusively infecting humans. We propose an initiative to resolve disputed origins of major diseases, and a global early warning system to monitor pathogens infecting individuals exposed to wild animals. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nature05775) contains supplementary material, which is available to authorized users.

Nature2007       CORD-19
557Microarray-based detection and genotyping of viral pathogens  

N/A

Proc Natl Acad Sci U S A2002       CORD-19
558Anxiety and Sleep Disturbances Among Healthcare Workers During the COVID-19 Pandemic in India: Cross-Sectional Online Survey  

BACKGROUND: The COVID-19 pandemic caused by SARS-CoV-2 has become a serious concern among the global medical community and has resulted in an unprecedented psychological impact on health care workers, who were already working under stressful conditions. OBJECTIVE: In this study, we aimed to evaluate and measure the effects of the COVID-19 pandemic on the anxiety levels and sleep quality among health care workers in India, as well as to determine how the unavailability of personal protective equipment affects their willingness to provide patient-related care. METHODS: We conducted an online cross-sectional study using piloted, structured questionnaires with self-reported responses from 368 volunteer male and female health care workers in India. Study participants were identified through social networking platforms such as Facebook and WhatsApp. The survey evaluated the participants’ degree of signs and symptoms of anxiety and sleep quality based on the 7-item Generalized Anxiety Disorder (GAD-7) scale and single-item Sleep Quality Scale, respectively. Information on the availability of personal protective equipment was collected based on responses to relevant survey questions. RESULTS: The majority of health care workers (126/368, 34.2%) were in the age group 45-60 years, and 52.2% (192/368) were doctors. Severe anxiety (ie, GAD-7 score >10) was observed among 7.3% (27/368) health care workers, whereas moderate, mild, and minimal anxiety was observed among 12.5% (46/368), 29.3% (108/368), and 50.8% (187/368) health care workers, respectively. Moreover, 31.5% (116/368) of the health care workers had poor-to-fair sleep quality (ie, scores <6). Univariate analysis showed female gender and inadequate availability of personal protective equipment was significantly associated with higher anxiety levels (P=.01 for both). Sleep disturbance was significantly associated with age <30 years (P=.04) and inadequate personal protective equipment (P<.001). Multivariable analysis showed that poorer quality of sleep was associated with higher anxiety levels (P<.001). CONCLUSIONS: The COVID-19 pandemic has potentially caused significant levels of anxiety and sleep disturbances among health care workers, particularly associated with the female gender, younger age group, and inadequate availability of personal protective equipment. These factors put health care workers at constant risk of contracting the infection themselves or transmitting it to their families. Early identification of at-risk health care workers and implementation of situation-tailored mitigation measures could help alleviate the risk of long-term, serious psychological sequelae as well as reduce current anxiety levels among health care workers.

JMIR Public Health Surveill2020       LitCov and CORD-19
559Supporting individuals with intellectual and developmental disability during the first One Hundred Days of the COVID-19 outbreak in the USA  

BACKGROUND: It is unknown how the novel Coronavirus SARS‐CoV‐2, the cause of the current acute respiratory illness COVID‐19 pandemic that has infected millions of people, affects people with intellectual and developmental disability (IDD). The aim of this study is to describe how individuals with IDD have been affected in the first 100 days of the COVID‐19 pandemic. METHODS: Shortly after the first COVID‐19 case was reported in the USA, our organisation, which provides continuous support for over 11 000 individuals with IDD, assembled an outbreak committee composed of senior leaders from across the health care organisation. The committee led the development and deployment of a comprehensive COVID‐19 prevention and suppression strategy, utilising current evidence‐based practice, while surveilling the global and local situation daily. We implemented enhanced infection control procedures across 2400 homes, which were communicated to our employees using multi‐faceted channels including an electronic resource library, mobile and web applications, paper postings in locations, live webinars and direct mail. Using custom‐built software applications enabling us to track patient, client and employee cases and exposures, we leveraged current public health recommendations to identify cases and to suppress transmission, which included the use of personal protective equipment. A COVID‐19 case was defined as a positive nucleic acid test for SARS‐CoV‐2 RNA. RESULTS: In the 100‐day period between 20 January 2020 and 30 April 2020, we provided continuous support for 11 540 individuals with IDD. Sixty‐four per cent of the individuals were in residential, community settings, and 36% were in intermediate care facilities. The average age of the cohort was 46 ± 12 years, and 60% were male. One hundred twenty‐two individuals with IDD were placed in quarantine for exhibiting symptoms and signs of acute infection such as fever or cough. Sixty‐six individuals tested positive for SARS‐CoV‐2, and their average age was 50. The positive individuals were located in 30 different homes (1.3% of total) across 14 states. Fifteen homes have had single cases, and 15 have had more than one case. Fifteen COVID‐19‐positive individuals were hospitalised. As of 30 April, seven of the individuals hospitalised have been discharged back to home and are recovering. Five remain hospitalised, with three improving and two remaining in intensive care and on mechanical ventilation. There have been three deaths. We found that among COVID‐19‐positive individuals with IDD, a higher number of chronic medical conditions and male sex were characteristics associated with a greater likelihood of hospitalisation. CONCLUSIONS: In the first 100 days of the COVID‐19 outbreak in the USA, we observed that people with IDD living in congregate care settings can benefit from a coordinated approach to infection control, case identification and cohorting, as evidenced by the low relative case rate reported. Male individuals with higher numbers of chronic medical conditions were more likely to be hospitalised, while most younger, less chronically ill individuals recovered spontaneously at home.

J Intellect Disabil Res2020       LitCov and CORD-19
560Development of a Fluorescence-Based, High-Throughput SARS-CoV-2 3CLpro Reporter Assay  

In late 2019, a human coronavirus, now known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged, likely from a zoonotic reservoir. This virus causes COVID-19, has infected millions of people, and has led to hundreds of thousands of deaths across the globe. While the best interventions to control and ultimately stop the pandemic are prophylactic vaccines, antiviral therapeutics are important to limit morbidity and mortality in those already infected. At this time, only one FDA-approved anti-SARS-CoV-2 antiviral drug, remdesivir, is available, and unfortunately, its efficacy appears to be limited. Thus, the identification of new and efficacious antivirals is of the highest importance. In order to facilitate rapid drug discovery, flexible, sensitive, and high-throughput screening methods are required. With respect to drug targets, most attention is focused on either the viral RNA-dependent RNA polymerase or the main viral protease, 3CL(pro). 3CL(pro) is an attractive target for antiviral therapeutics, as it is essential for processing newly translated viral proteins and the viral life cycle cannot be completed without protease activity. In this work, we report a new assay to identify inhibitors of 3CL(pro). Our reporter is based on a green fluorescent protein (GFP)-derived protein that fluoresces only after cleavage by 3CL(pro). This experimentally optimized reporter assay allows for antiviral drug screening in human cell culture at biosafety level 2 (BSL2) with high-throughput compatible protocols. Using this screening approach in combination with existing drug libraries may lead to the rapid identification of novel antivirals to suppress SARS-CoV-2 replication and spread. IMPORTANCE The COVID-19 pandemic has already led to more than 700,000 deaths and innumerable changes to daily life worldwide. Along with development of a vaccine, identification of effective antivirals to treat infected patients is of the highest importance. However, rapid drug discovery requires efficient methods to identify novel compounds that can inhibit the virus. In this work, we present a method for identifying inhibitors of the SARS-CoV-2 main protease, 3CL(pro). This reporter-based assay allows for antiviral drug screening in human cell culture at biosafety level 2 (BSL2) with high-throughput compatible sample processing and analysis. This assay may help identify novel antivirals to control the COVID-19 pandemic.

J Virol2020       LitCov and CORD-19
561ViPR: an open bioinformatics database and analysis resource for virology research  

The Virus Pathogen Database and Analysis Resource (ViPR, www.ViPRbrc.org) is an integrated repository of data and analysis tools for multiple virus families, supported by the National Institute of Allergy and Infectious Diseases (NIAID) Bioinformatics Resource Centers (BRC) program. ViPR contains information for human pathogenic viruses belonging to the Arenaviridae, Bunyaviridae, Caliciviridae, Coronaviridae, Flaviviridae, Filoviridae, Hepeviridae, Herpesviridae, Paramyxoviridae, Picornaviridae, Poxviridae, Reoviridae, Rhabdoviridae and Togaviridae families, with plans to support additional virus families in the future. ViPR captures various types of information, including sequence records, gene and protein annotations, 3D protein structures, immune epitope locations, clinical and surveillance metadata and novel data derived from comparative genomics analysis. Analytical and visualization tools for metadata-driven statistical sequence analysis, multiple sequence alignment, phylogenetic tree construction, BLAST comparison and sequence variation determination are also provided. Data filtering and analysis workflows can be combined and the results saved in personal ‘Workbenches’ for future use. ViPR tools and data are available without charge as a service to the virology research community to help facilitate the development of diagnostics, prophylactics and therapeutics for priority pathogens and other viruses.

Nucleic Acids Res2011       CORD-19
562The COVID-19 pandemic  

N/A

Crit Rev Clin Lab Sci2020       LitCov and CORD-19
563Vaccine Candidates against Coronavirus Infections. Where Does COVID-19 Stand?  

Seven years after the Middle East respiratory syndrome (MERS) outbreak, a new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) made its first appearance in a food market in Wuhan, China, drawing an entirely new course to our lives. As the virus belongs to the same genus of MERS and SARS, researchers have been trying to draw lessons from previous outbreaks to find a potential cure. Although there were five Phase I human vaccine trials against SARS and MERS, the lack of data in humans provided us with limited benchmarks that could help us design a new vaccine for Coronavirus disease 2019 (COVID-19). In this review, we showcase the similarities in structures of virus components between SARS-CoV, MERS-CoV, and SARS-CoV-2 in areas relevant to vaccine design. Using the ClinicalTrials.gov and World Health Organization (WHO) databases, we shed light on the 16 current approved clinical trials worldwide in search for a COVID-19 vaccine. The different vaccine platforms being tested are Bacillus Calmette–Guérin (BCG) vaccines, DNA and RNA-based vaccines, inactivated vaccines, protein subunits, and viral vectors. By thoroughly analyzing different trials and platforms, we also discuss the advantages and disadvantages of using each type of vaccine and how they can contribute to the design of an adequate vaccine for COVID-19. Studying past efforts invested in conducting vaccine trials for MERS and SARS will provide vital insights regarding the best approach to designing an effective vaccine against COVID-19.

Viruses2020       LitCov and CORD-19
564Factors associated with mental health outcomes across healthcare settings in Oman during COVID-19: frontline vs non-frontline healthcare workers  

OBJECTIVE: This study aims to assess and compare demographic and psychological factors and sleep status of frontline healthcare workers (HCWs) in relation to non-frontline HCWs. DESIGN, SETTINGS, PARTICIPANTS AND OUTCOMES: This cross-sectional study was conducted from 8 April 2020 to 17 April 2020 using an online survey across varied healthcare settings in Oman accruing 1139 HCWs. The primary and secondary outcomes were mental health status and sociodemographic data, respectively. Mental health status was assessed using the Depression, Anxiety, and Stress Scale (DASS-21), and insomnia was evaluated by the Insomnia Severity Index. Samples were categorised into the frontline and non-frontline groups. χ(2) and t-tests were used to compare groups by demographic data. The Mantel-Haenszel OR was used to compare groups by mental health outcomes adjusted by all sociodemographic factors. RESULTS: This study included 1139 HCWs working in Oman. While working during the pandemic period, a total of 368 (32.3%), 388 (34.1%), 271 (23.8%) and 211 (18.5%) respondents were reported to have depression, anxiety, stress and insomnia, respectively. HCWs in the frontline group were 1.5 times more likely to report anxiety (OR=1.557, p=0.004), stress (OR=1.506, p=0.016) and insomnia (OR=1.586, p=0.013) as compared with those in the non-frontline group. No significant differences in depression status were found between the frontline and non-frontline groups (p=0.201). CONCLUSIONS: To our knowledge, this is the first study to explore the differential impacts of the COVID-19 pandemic on different grades of HCWs. This study suggests that frontline HCWs are disproportionally affected compared to non-frontline HCWs, with managing sleep–wake cycles and anxiety symptoms being highly endorsed among frontline HCWs. As psychosocial interventions are likely to be constrained owing to the pandemic, mental healthcare must first be directed to frontline HCWs.

BMJ Open2020       LitCov and CORD-19
565Coagulopathy and Antiphospholipid Antibodies in Patients with Covid-19  

The authors describe a 69-year-old man with Covid-19 diagnosed in January 2020 in Wuhan, China, along with two other critically ill patients with Covid-19 who were also seen in the same intensive care unit. Coagulopathy and antiphospholipid antibodies were seen in all three patients.

N Engl J Med2020       LitCov and CORD-19
566SARS-CoV-2 strategically mimics proteolytic activation of human ENaC  

Molecular mimicry is an evolutionary strategy adopted by viruses to exploit the host cellular machinery. We report that SARS-CoV-2 has evolved a unique S1/S2 cleavage site, absent in any previous coronavirus sequenced, resulting in the striking mimicry of an identical FURIN-cleavable peptide on the human epithelial sodium channel α-subunit (ENaC-α). Genetic alteration of ENaC-α causes aldosterone dysregulation in patients, highlighting that the FURIN site is critical for activation of ENaC. Single cell RNA-seq from 66 studies shows significant overlap between expression of ENaC-α and the viral receptor ACE2 in cell types linked to the cardiovascular-renal-pulmonary pathophysiology of COVID-19. Triangulating this cellular characterization with cleavage signatures of 178 proteases highlights proteolytic degeneracy wired into the SARS-CoV-2 lifecycle. Evolution of SARS-CoV-2 into a global pandemic may be driven in part by its targeted mimicry of ENaC-α, a protein critical for the homeostasis of airway surface liquid, whose misregulation is associated with respiratory conditions.

Elife2020       LitCov and CORD-19
567COVID-19 and mental health: A review of the existing literature  

The COVID-19 pandemic is a major health crisis affecting several nations, with over 720,000 cases and 33,000 confirmed deaths reported to date. Such widespread outbreaks are associated with adverse mental health consequences. Keeping this in mind, existing literature on the COVID-19 outbreak pertinent to mental health was retrieved via a literature search of the PubMed database. Published articles were classified according to their overall themes and summarized. Preliminary evidence suggests that symptoms of anxiety and depression (16–28%) and self-reported stress (8%) are common psychological reactions to the COVID-19 pandemic, and may be associated with disturbed sleep. A number of individual and structural variables moderate this risk. In planning services for such populations, both the needs of the concerned people and the necessary preventive guidelines must be taken into account. The available literature has emerged from only a few of the affected countries, and may not reflect the experience of persons living in other parts of the world. In conclusion, subsyndromal mental health problems are a common response to the COVID-19 pandemic. There is a need for more representative research from other affected countries, particularly in vulnerable populations.

Asian J Psychiatr2020       LitCov and CORD-19
568Effect of Pfizer/BioNTech and Oxford/AstraZeneca vaccines against COVID-19 morbidity and mortality in real-world settings at countrywide vaccination campaign in Saudi Arabia  

N/A

Eur Rev Med Pharmacol Sci2021       LitCov and CORD-19
569Severe acute respiratory syndrome vaccine development: experiences of vaccination against avian infectious bronchitis coronavirus  

Vaccines against infectious bronchitis of chickens (Gallus gallus domesticus) have arguably been the most successful, and certainly the most widely used, of vaccines for diseases caused by coronaviruses, the others being against bovine, canine, feline and porcine coronaviruses. Infectious bronchitis virus (IBV), together with the genetically related coronaviruses of turkey (Meleagris gallopavo) and ring-necked pheasant (Phasianus colchicus), is a group 3 coronavirus, Severe acute respiratory syndrome (SARS) coronavirus being tentatively in group 4, the other known mammalian coronaviruses being in groups 1 and 2. IBV replicates not only in respiratory tissues (including the nose, trachea, lungs and airsacs, causing respiratory disease), but also in the kidney (associated with minor or major nephritis), oviduct, and in many parts of the alimentary tract—the oesophagus, proventriculus, duodenum, jejunum, bursa of Fabricius, caecal tonsils, rectum and cloaca, usually without clinical effects. The virus can persist, being re-excreted at the onset of egg laying (4 to 5 months of age), believed to be a consequence of the stress of coming into lay. Genetic lines of chickens differ in the extent to which IBV causes mortality in chicks, and in respect of clearance of the virus after the acute phase. Live attenuated (by passage in chicken embryonated eggs) IBV strains were introduced as vaccines in the 1950s, followed a couple of decades later by inactivated vaccines for boosting protection in egg-laying birds. Live vaccines are usually applied to meat-type chickens at 1 day of age. In experimental situations this can result in sterile immunity when challenged by virulent homologous virus. Although 100% of chickens may be protected (against clinical signs and loss of ciliary activity in trachea), sometimes 10% of vaccinated chicks may not respond with a protective immune response. Protection is short lived, the start of the decline being apparent 9 weeks after vaccination with vaccines based on highly attenuated strains. IBV exists as scores of serotypes (defined by the neutralization test), cross-protection often being poor. Consequently, chickens may be re-vaccinated, with the same or another serotype, two or three weeks later. Single applications of inactivated virus has generally led to protection of <50% of chickens. Two applications have led to 90 to 100% protection in some reports, but remaining below 50% in others. In practice in the field, inactivated vaccines are used in laying birds that have previously been primed with two or three live attenuated virus vaccinations. This increases protection of the laying birds against egg production losses and induces a sustained level of serum antibody, which is passed to progeny. The large spike glycoprotein (S) comprises a carboxy-terminal S2 subunit (approximately 625 amino acid residues), which anchors S in the virus envelope, and an amino-terminal S1 subunit (approximately 520 residues), believed to largely form the distal bulbous part of S. The S1 subunit (purified from IBV virus, expressed using baculovirus or expressed in birds from a fowlpoxvirus vector) induced virus neutralizing antibody. Although protective immune responses were induced, multiple inoculations were required and the percentage of protected chickens was too low (<50%) for commercial application. Remarkably, expression of S1 in birds using a non-pathogenic fowl adenovirus vector induced protection in 90% and 100% of chickens in two experiments. Differences of as little as 5% between the S1 sequences can result in poor cross-protection. Differences in S1 of 2 to 3% (10 to 15 amino acids) can change serotype, suggesting that a small number of epitopes are immunodominant with respect to neutralizing antibody. Initial studies of the role of the IBV nucleocapsid protein (N) in immunity suggested that immunization with bacterially expressed N, while not inducing protection directly, improved the induction of protection by a subsequent inoculation with inactivated IBV. In another study, two intramuscular immunizations of a plasmid expressing N induced protective immunity. The basis of immunity to IBV is not well understood. Serum antibody levels do not correlate with protection, although local antibody is believed to play a role. Adoptive transfer of IBV-infection-induced αβ T cells bearing CD8 antigen protected chicks from challenge infection. In conclusion, live attenuated IBV vaccines induce good, although short-lived, protection against homologous challenge, although a minority of individuals may respond poorly. Inactivated IBV vaccines are insufficiently efficacious when applied only once and in the absence of priming by live vaccine. Two applications of inactivated IBV are much more efficacious, although this is not a commercially viable proposition in the poultry industry. However, the cost and logistics of multiple application of a SARS inactivated vaccine would be more acceptable for the protection of human populations, especially if limited to targeted groups (e.g. health care workers and high-risk contacts). Application of a SARS vaccine is perhaps best limited to a minimal number of targeted individuals who can be monitored, as some vaccinated persons might, if infected by SARS coronavirus, become asymptomatic excretors of virus, thereby posing a risk to non-vaccinated people. Looking further into the future, the high efficacy of the fowl adenovirus vector expressing the IBV S1 subunit provides optimism for a live SARS vaccine, if that were deemed to be necessary, with the possibility of including the N protein gene.

Avian Pathol2003       CORD-19
570Psychosocial and Socio-Economic Crisis in Bangladesh Due to COVID-19 Pandemic: A Perception-Based Assessment  

Background: The spread of the COVID-19 pandemic, the partial lockdown, the disease intensity, weak governance in the healthcare system, insufficient medical facilities, unawareness, and the sharing of misinformation in the mass media has led to people experiencing fear and anxiety. The present study intended to conduct a perception-based analysis to get an idea of people's psychosocial and socio-economic crisis, and the possible environmental crisis, amidst the COVID-19 pandemic in Bangladesh. Methods: A perception-based questionnaire was put online for Bangladeshi citizens of 18 years and/or older. The sample size was 1,066 respondents. Datasets were analyzed through a set of statistical techniques including principal component and hierarchical cluster analysis. Results: There was a positive significant association between fear of the COVID-19 outbreak with the struggling healthcare system (p < 0.05) of the country. Also, there was a negative association between the fragile health system of Bangladesh and the government's ability to deal with the pandemic (p < 0.05), revealing the poor governance in the healthcare system. A positive association of shutdown and social distancing with the fear of losing one's own or a family members' life, influenced by a lack of healthcare treatment (p < 0.05), reveals that, due to the decision of shutting down normal activities, people may be experiencing mental and economic stress. However, a positive association of the socio-economic impact of the shutdown with poor people's suffering, the price hike of basic essentials, the hindering of formal education (p < 0.05), and the possibility of a severe socio-economic and health crisis will be aggravated. Moreover, there is a possibility of a climate change-induced disaster and infectious diseases like dengue during/after the COVID-19 situation, which will create severe food insecurity (p < 0.01) and a further healthcare crisis. Conclusions: The partial lockdown in Bangladesh due to the COVID-19 pandemic increased community transmission and worsened the healthcare crisis, economic burden, and loss of GDP despite the resuming of industrial operations. In society, it has created psychosocial and socio-economic insecurity among people due to the loss of lives and livelihoods. The government should take proper inclusive steps for risk assessment, communications, and financial stimulus toward the public to alleviate their fear and anxiety, and to take proper action to boost mental health and well-being.

Front Public Health2020       LitCov and CORD-19
571Enhanced Binding of SARS-CoV-2 Spike Protein to Receptor by Distal Polybasic Cleavage Sites  

[Image: see text] The receptor-binding domain (RBD) of the SARS-CoV-2 spike protein plays a crucial role in binding the human cell receptor ACE2 that is required for viral entry. Many studies have been conducted to target the structures of RBD–ACE2 binding and to design RBD-targeting vaccines and drugs. Nevertheless, mutations distal from the SARS-CoV-2 RBD also impact its transmissibility and antibody can target non-RBD regions, suggesting the incomplete role of the RBD region in the spike protein–ACE2 binding. Here, in order to elucidate distant binding mechanisms, we analyze complexes of ACE2 with the wild-type spike protein and with key mutants via large-scale all-atom explicit solvent molecular dynamics simulations. We find that though distributed approximately 10 nm away from the RBD, the SARS-CoV-2 polybasic cleavage sites enhance, via electrostatic interactions and hydration, the RBD–ACE2 binding affinity. A negatively charged tetrapeptide (GluGluLeuGlu) is then designed to neutralize the positively charged arginine on the polybasic cleavage sites. We find that the tetrapeptide GluGluLeuGlu binds to one of the three polybasic cleavage sites of the SARS-CoV-2 spike protein lessening by 34% the RBD–ACE2 binding strength. This significant binding energy reduction demonstrates the feasibility to neutralize RBD–ACE2 binding by targeting this specific polybasic cleavage site. Our work enhances understanding of the binding mechanism of SARS-CoV-2 to ACE2, which may aid the design of therapeutics for COVID-19 infection.

ACS Nano2020       LitCov and CORD-19
572Clinical characteristics and outcomes of hospitalised patients with COVID-19 treated in Hubei (epicentre) and outside Hubei (non-epicentre): a nationwide analysis of China  

BACKGROUND: During the outbreak of coronavirus disease 2019 (COVID-19), consistent and considerable differences in disease severity and mortality rate of patients treated in Hubei province compared to those in other parts of China has been observed. We sought to compare the clinical characteristics and outcomes of patients being treated inside and outside Hubei province, and explore the factors underlying these differences. METHODS: Collaborating with the National Health Commission, we established a retrospective cohort to study hospitalised COVID-19 cases in China. Clinical characteristics, the rate of severe events and deaths, and the time to critical illness (invasive ventilation or intensive care unit admission or death) were compared between patients in and outside of Hubei. The impact of Wuhan-related exposure (a presumed key factor that drove the severe situation in Hubei, as Wuhan is the epicenter as well the administrative center of Hubei province) and the duration between symptom onset and admission on prognosis were also determined. RESULTS: Upon data cut-off (Jan 31st, 2020), 1590 cases from 575 hospitals in 31 provincial administrative regions were collected (core cohort). The overall rate of severe cases and mortality was 16.0% and 3.2%, respectively. Patients in Hubei (predominantly with Wuhan-related exposure, 597/647, 92.3%) were older (mean: 49.7 versus 44.9 years), had more cases with comorbidity (32.9% versus 19.7%), higher symptomatic burden, abnormal radiologic manifestations, and, especially, a longer waiting time between symptom onset and admission (5.7 versus 4.5 days) compared with patients outside Hubei. Patients in Hubei [severe event rate 23.0% versus 11.1%, death rate 7.3% versus 0.3%, hazards ratio (HR) for critical illness 1.59, 95%CI 1.05–2.41] have a poorer prognosis compared with patients outside of Hubei after adjusting for age and comorbidity. However, among patients outside of Hubei, the duration from symptom onset to hospitalisation (mean: 4.4 versus 4.7 days) and prognosis (HR 0.84, 95%CI 0.40–1.80) were similar between patients with or without Wuhan-related exposure. In the overall population, the waiting time, but neither treated in Hubei nor Wuhan-related exposure, remained an independent prognostic factor (HR 1.05, 1.01–1.08). CONCLUSION: There were more severe cases and poorer outcomes for COVID-19 patients treated in Hubei, which might be attributed to the prolonged duration of symptom onset to hospitalisation in the epicenter. Future studies to determine the reason for delaying hospitalisation are warranted.

Eur Respir J2020       LitCov and CORD-19
573Plasma inflammatory cytokines and chemokines in severe acute respiratory syndrome  

Severe acute respiratory syndrome (SARS) is a recently emerged infectious disease caused by a novel coronavirus, but its immunopathological mechanisms have not yet been fully elucidated. We investigated changes in plasma T helper (Th) cell cytokines, inflammatory cytokines and chemokines in 20 patients diagnosed with SARS. Cytokine profile of SARS patients showed marked elevation of Th1 cytokine interferon (IFN)-γ, inflammatory cytokines interleukin (IL)-1, IL-6 and IL-12 for at least 2 weeks after disease onset, but there was no significant elevation of inflammatory cytokine tumour necrosis factor (TNF)-α, anti-inflammatory cytokine IL-10, Th1 cytokine IL-2 and Th2 cytokine IL-4. The chemokine profile demonstrated significant elevation of neutrophil chemokine IL-8, monocyte chemoattractant protein-1 (MCP-1), and Th1 chemokine IFN-γ-inducible protein-10 (IP-10). Corticosteroid reduced significantly IL-8, MCP-1 and IP-10 concentrations from 5 to 8 days after treatment (all P < 0·001). Together, the elevation of Th1 cytokine IFN-γ, inflammatory cytokines IL-1, IL-6 and IL-12 and chemokines IL-8, MCP-1 and IP-10 confirmed the activation of Th1 cell-mediated immunity and hyperinnate inflammatory response in SARS through the accumulation of monocytes/macrophages and neutrophils.

Clin Exp Immunol2004       CORD-19
574Deep Convolutional Neural Networks for Computer-Aided Detection: CNN Architectures, Dataset Characteristics and Transfer Learning  

Remarkable progress has been made in image recognition, primarily due to the availability of large-scale annotated datasets and deep convolutional neural networks (CNNs). CNNs enable learning data-driven, highly representative, hierarchical image features from sufficient training data. However, obtaining datasets as comprehensively annotated as ImageNet in the medical imaging domain remains a challenge. There are currently three major techniques that successfully employ CNNs to medical image classification: training the CNN from scratch, using off-the-shelf pre-trained CNN features, and conducting unsupervised CNN pre-training with supervised fine-tuning. Another effective method is transfer learning, i.e., fine-tuning CNN models pre-trained from natural image dataset to medical image tasks. In this paper, we exploit three important, but previously understudied factors of employing deep convolutional neural networks to computer-aided detection problems. We first explore and evaluate different CNN architectures. The studied models contain 5 thousand to 160 million parameters, and vary in numbers of layers. We then evaluate the influence of dataset scale and spatial image context on performance. Finally, we examine when and why transfer learning from pre-trained ImageNet (via fine-tuning) can be useful. We study two specific computer-aided detection (CADe) problems, namely thoraco-abdominal lymph node (LN) detection and interstitial lung disease (ILD) classification. We achieve the state-of-the-art performance on the mediastinal LN detection, and report the first five-fold cross-validation classification results on predicting axial CT slices with ILD categories. Our extensive empirical evaluation, CNN model analysis and valuable insights can be extended to the design of high performance CAD systems for other medical imaging tasks.

IEEE Trans Med Imaging2016       CORD-19
575In Vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxychloroquine for the Treatment of SARS-CoV-2  

BACKGROUND: The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) first broke out in Wuhan (China) and subsequently spread worldwide. Chloroquine has been sporadically used in treating SARS-CoV-2 infection. Hydroxychloroquine shares the same mechanism of action as chloroquine, but its more tolerable safety profile makes it the preferred drug to treat malaria and autoimmune conditions. We propose that the immunomodulatory effect of hydroxychloroquine also may be useful in controlling the cytokine storm that occurs late-phase in critically ill SARS-CoV-2 infected patients. Currently, there is no evidence to support the use of hydroxychloroquine in SARS-CoV-2 infection. METHODS: The pharmacological activity of chloroquine and hydroxychloroquine was tested using SARS-CoV-2 infected Vero cells. Physiologically-based pharmacokinetic models (PBPK) were implemented for both drugs separately by integrating their in vitro data. Using the PBPK models, hydroxychloroquine concentrations in lung fluid were simulated under 5 different dosing regimens to explore the most effective regimen whilst considering the drug’s safety profile. RESULTS: Hydroxychloroquine (EC(50)=0.72 μM) was found to be more potent than chloroquine (EC(50)=5.47 μM) in vitro. Based on PBPK models results, a loading dose of 400 mg twice daily of hydroxychloroquine sulfate given orally, followed by a maintenance dose of 200 mg given twice daily for 4 days is recommended for SARS-CoV-2 infection, as it reached three times the potency of chloroquine phosphate when given 500 mg twice daily 5 days in advance. CONCLUSIONS: Hydroxychloroquine was found to be more potent than chloroquine to inhibit SARS-CoV-2 in vitro.

Clin Infect Dis2020       LitCov and CORD-19
576Psychological distress, anxiety, family violence, suicidality and wellbeing in New Zealand during the COVID-19 lockdown: A cross-sectional study  

New Zealand’s early response to the novel coronavirus pandemic included a strict lockdown which eliminated community transmission of COVID-19. However, this success was not without cost, both economic and social. In our study, we examined the psychological wellbeing of New Zealanders during the COVID-19 lockdown when restrictions reduced social contact, limited recreation opportunities, and resulted in job losses and financial insecurity. We conducted an online panel survey of a demographically representative sample of 2010 adult New Zealanders in April 2020. The survey contained three standardised measures–the Kessler Psychological Distress Scale (K10), the GAD-7, and the Well-Being Index (WHO-5)–as well as questions designed specifically to measure family violence, suicidal ideation, and alcohol consumption. It also included items assessing positive aspects of the lockdown. Thirty percent of respondents reported moderate to severe psychological distress (K10), 16% moderate to high levels of anxiety, and 39% low wellbeing; well above baseline measures. Poorer outcomes were seen among young people and those who had lost jobs or had less work, those with poor health status, and who had past diagnoses of mental illness. Suicidal ideation was reported by 6%, with 2% reporting making plans for suicide and 2% reporting suicide attempts. Suicidality was highest in those aged 18–34. Just under 10% of participants had directly experienced some form of family harm over the lockdown period. However, not all consequences of the lockdown were negative, with 62% reporting ‘silver linings’, which included enjoying working from home, spending more time with family, and a quieter, less polluted environment. New Zealand’s lockdown successfully eliminated COVID-19 from the community, but our results show this achievement brought a significant psychological toll. Although much of the debate about lockdown measures has focused on their economic effects, our findings emphasise the need to pay equal attention to their effects on psychological wellbeing.

PLoS One2020       LitCov and CORD-19
577Technical guidelines for seasonal influenza vaccination in China (2020-2021)  

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Zhonghua Liu Xing Bing Xue Za 2020       LitCov and CORD-19
578Neurologic Features in Severe SARS-CoV-2 Infection  

N Engl J Med2020       LitCov and CORD-19
579Outbreak of pneumonia of unknown etiology in Wuhan, China: The mystery and the miracle  

Since December 2019, a total of 41 cases of pneumonia of unknown etiology have been confirmed in Wuhan city, Hubei Province, China. Wuhan city is a major transportation hub with a population of more than 11 million people. Most of the patients visited a local fish and wild animal market last month. At a national press conference held today, Dr. Jianguo Xu, an academician of the Chinese Academy of Engineering, who led a scientific team announced that a new-type coronavirus, tentatively named by World Health Organization as the 2019-new coronavirus (2019-nCoV), had caused this outbreak (1).

J Med Virol2020       LitCov and CORD-19
580COVID-19 Is a Multifaceted Challenging Pandemic Which Needs Urgent Public Health Interventions  

Until less than two decades ago, all known human coronaviruses (CoV) caused diseases so mild that they did not stimulate further advanced CoV research. In 2002 and following years, the scenario changed dramatically with the advent of the new more pathogenic CoVs, including Severe Acute Respiratory Syndome (SARS-CoV-1), Middle Eastern respiratory syndrome (MERS)-CoV, and the new zoonotic SARS-CoV-2, likely originated from bat species and responsible for the present coronavirus disease (COVID-19), which to date has caused 15,581,007 confirmed cases and 635,173 deaths in 208 countries, including Italy. SARS-CoV-2 transmission is mainly airborne via droplets generated by symptomatic patients, and possibly asymptomatic individuals during incubation of the disease, although for the latter, there are no certain data yet. However, research on asymptomatic viral infection is currently ongoing worldwide to elucidate the real prevalence and mortality of the disease. From a clinical point of view, COVID-19 would be defined as “COVID Planet “ because it presents as a multifaceted disease, due to the large number of organs and tissues infected by the virus. Overall, based on the available published data, 80.9% of patients infected by SARS-CoV-2 develop a mild disease/infection, 13.8% severe pneumonia, 4.7% respiratory failure, septic shock, or multi-organ failure, and 3% of these cases are fatal, but mortality parameter is highly variable in different countries. Clinically, SARS-CoV-2 causes severe primary interstitial viral pneumonia and a “cytokine storm syndrome”, characterized by a severe and fatal uncontrolled systemic inflammatory response triggered by the activation of interleukin 6 (IL-6) with development of endothelitis and generalized thrombosis that can lead to organ failure and death. Risk factors include advanced age and comorbidities including hypertension, diabetes, and cardiovascular disease. Virus entry occurs via binding the angiotensin-converting enzyme 2 (ACE2) receptor present in almost all tissues and organs through the Spike (S) protein. Currently, SARS-CoV-2 infection is prevented by the use of masks, social distancing, and improved hand hygiene measures. This review summarizes the current knowledge on the main biological and clinical features of the SARS-CoV-2 pandemic, also focusing on the principal measures taken in some Italian regions to face the emergency and on the most important treatments used to manage the COVID-19 pandemic.

Microorganisms2020       LitCov and CORD-19
581Prevalence of depression, anxiety and insomnia among healthcare workers during the COVID-19 pandemic: A systematic review and meta-analysis  

Abstract Background COVID-19 pandemic has the potential to significantly affect the mental health of healthcare workers (HCWs), who stand in the frontline of this crisis. It is, therefore, an immediate priority to monitor rates of mood, sleep and other mental health issues in order to understand mediating factors and inform tailored interventions. The aim of this review is to synthesize and analyze existing evidence on the prevalence of depression, anxiety and insomnia among HCWs during the Covid-19 outbreak. Methods A systematic search of literature databases was conducted up to April 17th, 2020. Two reviewers independently assessed full-text articles according to predefined criteria. Risk of bias for each individual study was assessed and data pooled using random-effects meta-analyses to estimate the prevalence of specific mental health problems. The review protocol is registered in PROSPERO and is available online. Findings Thirteen studies were included in the analysis with a combined total of 33062 participants. Anxiety was assessed in 12 studies, with a pooled prevalence of 23·2% and depression in 10 studies, with a prevalence rate of 22·8%. A subgroup analysis revealed gender and occupational differences with female HCPs and nurses exhibiting higher rates of affective symptoms compared to male and medical staff respectively. Finally, insomnia prevalence was estimated at 38·9% across 4 studies. Interpretation Early evidence suggests that a considerable proportion of HCWs experience mood and sleep disturbances during this outbreak, stressing the need to establish ways to mitigate mental health risks and adjust interventions under pandemic conditions.

Brain Behav Immun2020       LitCov and CORD-19
582Feasibility of controlling COVID-19 outbreaks by isolation of cases and contacts  

BACKGROUND: Isolation of cases and contact tracing is used to control outbreaks of infectious diseases, and has been used for coronavirus disease 2019 (COVID-19). Whether this strategy will achieve control depends on characteristics of both the pathogen and the response. Here we use a mathematical model to assess if isolation and contact tracing are able to control onwards transmission from imported cases of COVID-19. METHODS: We developed a stochastic transmission model, parameterised to the COVID-19 outbreak. We used the model to quantify the potential effectiveness of contact tracing and isolation of cases at controlling a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-like pathogen. We considered scenarios that varied in the number of initial cases, the basic reproduction number (R(0)), the delay from symptom onset to isolation, the probability that contacts were traced, the proportion of transmission that occurred before symptom onset, and the proportion of subclinical infections. We assumed isolation prevented all further transmission in the model. Outbreaks were deemed controlled if transmission ended within 12 weeks or before 5000 cases in total. We measured the success of controlling outbreaks using isolation and contact tracing, and quantified the weekly maximum number of cases traced to measure feasibility of public health effort. FINDINGS: Simulated outbreaks starting with five initial cases, an R(0) of 1·5, and 0% transmission before symptom onset could be controlled even with low contact tracing probability; however, the probability of controlling an outbreak decreased with the number of initial cases, when R(0) was 2·5 or 3·5 and with more transmission before symptom onset. Across different initial numbers of cases, the majority of scenarios with an R(0) of 1·5 were controllable with less than 50% of contacts successfully traced. To control the majority of outbreaks, for R(0) of 2·5 more than 70% of contacts had to be traced, and for an R(0) of 3·5 more than 90% of contacts had to be traced. The delay between symptom onset and isolation had the largest role in determining whether an outbreak was controllable when R(0) was 1·5. For R(0) values of 2·5 or 3·5, if there were 40 initial cases, contact tracing and isolation were only potentially feasible when less than 1% of transmission occurred before symptom onset. INTERPRETATION: In most scenarios, highly effective contact tracing and case isolation is enough to control a new outbreak of COVID-19 within 3 months. The probability of control decreases with long delays from symptom onset to isolation, fewer cases ascertained by contact tracing, and increasing transmission before symptoms. This model can be modified to reflect updated transmission characteristics and more specific definitions of outbreak control to assess the potential success of local response efforts. FUNDING: Wellcome Trust, Global Challenges Research Fund, and Health Data Research UK.

Lancet Glob Health2020       LitCov and CORD-19
583Severe Outcomes Among Patients with COVID-19-United States, February 12-March 16, 2020  

Globally, approximately 170,000 confirmed cases of coronavirus disease 2019 (COVID-19) caused by the 2019 novel coronavirus (SARS-CoV-2) have been reported, including an estimated 7,000 deaths in approximately 150 countries (1). On March 11, 2020, the World Health Organization declared the COVID-19 outbreak a pandemic (2). Data from China have indicated that older adults, particularly those with serious underlying health conditions, are at higher risk for severe COVID-19-associated illness and death than are younger persons (3). Although the majority of reported COVID-19 cases in China were mild (81%), approximately 80% of deaths occurred among adults aged ≥60 years; only one (0.1%) death occurred in a person aged ≤19 years (3). In this report, COVID-19 cases in the United States that occurred during February 12-March 16, 2020 and severity of disease (hospitalization, admission to intensive care unit [ICU], and death) were analyzed by age group. As of March 16, a total of 4,226 COVID-19 cases in the United States had been reported to CDC, with multiple cases reported among older adults living in long-term care facilities (4). Overall, 31% of cases, 45% of hospitalizations, 53% of ICU admissions, and 80% of deaths associated with COVID-19 were among adults aged ≥65 years with the highest percentage of severe outcomes among persons aged ≥85 years. In contrast, no ICU admissions or deaths were reported among persons aged ≤19 years. Similar to reports from other countries, this finding suggests that the risk for serious disease and death from COVID-19 is higher in older age groups.

MMWR Morb Mortal Wkly Rep2020       LitCov and CORD-19
584Effectiveness of eHealth interventions for the promotion of physical activity in older adults: a systematic review protocol  

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Syst Rev2016       CORD-19
585Kidney disease is associated with in-hospital death of patients with COVID-19  

In December 2019, a coronavirus 2019 (COVID-19) disease outbreak occurred in Wuhan, Hubei Province, China, and rapidly spread to other areas worldwide. Although diffuse alveolar damage and acute respiratory failure were the main features, the involvement of other organs needs to be explored. Since information on kidney disease in patients with COVID-19 is limited, we determined the prevalence of acute kidney injury (AKI) in patients with COVID-19. Further, we evaluated the association between markers of abnormal kidney function and death in patients with COVID-19. This was a prospective cohort study of 701 patients with COVID-19 admitted in a tertiary teaching hospital that also encompassed three affiliates following this major outbreak in Wuhan in 2020 of whom 113 (16.1%) died in hospital. Median age of the patients was 63 years (interquartile range, 50-71), including 367 men and 334 women. On admission, 43.9% of patients had proteinuria and 26.7% had hematuria. The prevalence of elevated serum creatinine, elevated blood urea nitrogen and estimated glomerular filtration under 60 ml/min/1.73m(2) were 14.4, 13.1 and 13.1%, respectively. During the study period, AKI occurred in 5.1% patients. Kaplan-Meier analysis demonstrated that patients with kidney disease had a significantly higher risk for in-hospital death. Cox proportional hazard regression confirmed that elevated baseline serum creatinine (hazard ratio: 2.10, 95% confidence interval: 1.36-3.26), elevated baseline blood urea nitrogen (3.97, 2.57-6.14), AKI stage 1 (1.90, 0.76-4.76), stage 2 (3.51, 1.49-8.26), stage 3 (4.38, 2.31-8.31), proteinuria 1+ (1.80, 0.81-4.00), 2+∼3+ (4.84, 2.00-11.70), and hematuria 1+ (2.99, 1.39-6.42), 2+∼3+ (5.56,2.58- 12.01) were independent risk factors for in-hospital death after adjusting for age, sex, disease severity, comorbidity and leukocyte count. Thus, our findings show the prevalence of kidney disease on admission and the development of AKI during hospitalization in patients with COVID-19 is high and is associated with in-hospital mortality. Hence, clinicians should increase their awareness of kidney disease in patients with severe COVID-19.

Kidney Int2020       LitCov and CORD-19
586A previously undescribed coronavirus associated with respiratory disease in humans  

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Proc Natl Acad Sci U S A2004       CORD-19
587Improved Molecular Diagnosis of COVID-19 by the Novel, Highly Sensitive and Specific COVID-19-RdRp/Hel Real-Time Reverse Transcription-PCR Assay Validated In Vitro and with Clinical Specimens  

On 31 December 2019, the World Health Organization was informed of a cluster of cases of pneumonia of unknown etiology in Wuhan, China. Subsequent investigations identified a novel coronavirus, now named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), from the affected patients. Highly sensitive and specific laboratory diagnostics are important for controlling the rapidly evolving SARS-CoV-2-associated coronavirus disease 2019 (COVID-19) epidemic. In this study, we developed and compared the performance of three novel real-time reverse transcription-PCR (RT-PCR) assays targeting the RNA-dependent RNA polymerase (RdRp)/helicase (Hel), spike (S), and nucleocapsid (N) genes of SARS-CoV-2 with that of the reported RdRp-P2 assay, which is used in >30 European laboratories. Among the three novel assays, the COVID-19-RdRp/Hel assay had the lowest limit of detection in vitro (1.8 50% tissue culture infective doses [TCID(50)]/ml with genomic RNA and 11.2 RNA copies/reaction with in vitro RNA transcripts). Among 273 specimens from 15 patients with laboratory-confirmed COVID-19 in Hong Kong, 77 (28.2%) were positive by both the COVID-19-RdRp/Hel and RdRp-P2 assays. The COVID-19-RdRp/Hel assay was positive for an additional 42 RdRp-P2-negative specimens (119/273 [43.6%] versus 77/273 [28.2%]; P < 0.001), including 29/120 (24.2%) respiratory tract specimens and 13/153 (8.5%) non-respiratory tract specimens. The mean viral load of these specimens was 3.21 × 10(4) RNA copies/ml (range, 2.21 × 10(2) to 4.71 × 10(5) RNA copies/ml). The COVID-19-RdRp/Hel assay did not cross-react with other human-pathogenic coronaviruses and respiratory pathogens in cell culture and clinical specimens, whereas the RdRp-P2 assay cross-reacted with SARS-CoV in cell culture. The highly sensitive and specific COVID-19-RdRp/Hel assay may help to improve the laboratory diagnosis of COVID-19.

J Clin Microbiol2020       LitCov and CORD-19
588The importance of vitamin d metabolism as a potential prophylactic, immunoregulatory and neuroprotective treatment for COVID-19  

1. Vitamin D might aid in preventing SARS-CoV-2 infection: Vitamin D: Overview of Renal and Extra-renal metabolism and regulation. Vitamin D: Overview of molecular mechanism and multifaceted functions beyond skeletal homeostasis. Vitamin D: Overview of local immunomodulation in human infectious diseases. Anti-viral infection. Anti-malaria and anti-systemic lupus erythematosus (SLE). 2. Vitamin D might act as a strong immunosuppressant inhibiting cytokine release syndrome in COVID-19: Vitamin D: Suppression of key pro-inflammatory pathways including nuclear factor kappa B (NF-kB), interleukin-6 (IL-6), and tumor necrosis factor (TNF). 3. Vitamin D might prevent loss of neural sensation in COVID-19 by stimulating expression of neurotrophins like Nerve Growth Factor (NGF): Vitamin D: Induction of key neurotrophic factors. .

J Transl Med2020       LitCov and CORD-19
589Frequency and Distribution of Chest Radiographic Findings in COVID-19 Positive Patients  

BACKGROUND: Current COVID-19 radiological literature is dominated by CT and a detailed description of chest x-ray (CXR) appearances in relation to the disease time course is lacking. PURPOSE: To describe the time course and severity of the CXR findings of COVID-19 and correlate these with real time reverse transcription polymerase chain reaction (RT-PCR) testing for SARS-Cov-2 nucleic acid. MATERIALS AND METHODS: Retrospective study of COVID-19 patients with RT-PCR confirmation and CXRs admitted across 4 hospitals evaluated between January and March 2020. Baseline and serial CXRs (total 255 CXRs) were reviewed along with RT-PCRs. Correlation with concurrent CTs (total 28 CTs) was made when available. Two radiologists scored each CXR in consensus for: consolidation, ground glass opacity (GGO), location and pleural fluid. A severity index was determined for each lung. The lung scores were summed to produce the final severity score. RESULTS: There were 64 patients (26 men, mean age 56±19 years). Of these, 58, 44 and 38 patients had positive initial RT-PCR (91%, [CI: 81-96%]), abnormal baseline CXR (69%, [CI: 56-80%]) and positive initial RT-PCR with abnormal baseline CXR (59 [CI:46-71%]) respectively. Six patients (9%) showed CXR abnormalities before eventually testing positive on RT-PCR. Sensitivity of initial RT-PCR (91% [95% CI: 83-97%]) was higher than baseline CXR (69% [95% CI: 56-80%]) (p = 0.009). Radiographic (mean 6 ± 5 days) and virologic recovery (mean 8 ± 6 days) were not significantly different (p= 0.33). Consolidation was the most common finding (30/64, 47%), followed by GGO (21/64, 33%). CXR abnormalities had a peripheral (26/64, 41%) and lower zone distribution (32/64, 50%) with bilateral involvement (32/64, 50%). Pleural effusion was uncommon (2/64, 3%). The severity of CXR findings peaked at 10-12 days from the date of symptom onset. CONCLUSION: Chest x-ray findings in COVID-19 patients frequently showed bilateral lower zone consolidation which peaked at 10-12 days from symptom onset.

Radiology2020       LitCov and CORD-19
590SARS virus infection of cats and ferrets  

The reservoir of the coronavirus isolated from patients with severe acute respiratory syndrome (SARS)(1,2) is still unknown, but is suspected to have been a wild animal species. Here we show that ferrets (Mustela furo) and domestic cats (Felis domesticus) are susceptible to infection by SARS coronavirus (SCV) and that they can efficiently transmit the virus to previously uninfected animals that are housed with them. The observation that these two distantly related carnivores can so easily be infected with the virus indicates that the reservoir for this pathogen may involve a range of animal species. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/425915a) contains supplementary material, which is available to authorized users.

Nature2003       CORD-19
591Source of the COVID-19 pandemic: ecology and genetics of coronaviruses (Betacoronavirus: Coronaviridae) SARS-CoV, SARS-CoV-2 (subgenus Sarbecovirus) and MERS-CoV (subgenus Merbecovirus)  

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Vopr Virusol2020       LitCov and CORD-19
592REVISITING HEALTH INFORMATION TECHNOLOGY ETHICAL, LEGAL and SOCIAL ISSUES and EVALUATION: TELEHEALTH/TELEMEDICINE and COVID-19  

BACKGROUND: Information technologies have been vital during the COVID-19 pandemic. Telehealth and telemedicine services, especially, fulfilled their promise by allowing patients to receive advice and care at a distance, making it safer for all concerned. Over the preceding years, professional societies, governments, and scholars examined ethical, legal, and social issues (ELSI) related to telemedicine and telehealth. Primary concerns evident from reviewing this literature have been quality of care, access, consent, and privacy. OBJECTIVES: To identify and summarize ethical, legal, and social issues related to information technology in healthcare, as exemplified by telehealth and telemedicine. To expand on prior analyses and address gaps illuminated by the COVID-19 experience. To propose future research directions. METHODS: Literature was identified through searches, forward and backward citation chaining, and the author’s knowledge of scholars and works in the area. EU and professional organizations’ guidelines, and nineteen scholarly papers were examined and categories created to identify ethical, legal, and social issues they addressed. A synthesis matrix was developed to categorize issues addressed by each source. RESULTS: A synthesis matrix was developed and issues categorized as: quality of care, consent and autonomy, access to care and technology, legal and regulatory, clinician responsibilities, patient responsibilities, changed relationships, commercialization, policy, information needs, and evaluation, with subcategories that fleshed out each category. The literature primarily addressed quality of care, access, consent, and privacy. Other identified considerations were little discussed. These and newer concerns include: usability, tailoring services to each patient, curriculum and training, implementation, commercialization, and licensing and liability. The need for interoperability, data availability, cybersecurity, and informatics infrastructure also is more apparent. These issues are applicable to other information technologies in healthcare. CONCLUSIONS: Clinicians and organizations need updated guidelines for ethical use of telemedicine and telehealth care, and decision- and policy-makers need evidence to inform decisions. The variety of newly implemented telemedicine services is an on-going natural experiment presenting an unparalleled opportunity to develop an evidence-based way forward. The paper recommends evaluation using an applied ethics, context-sensitive approach that explores interactions among multiple factors and considerations. It suggests evaluation questions to investigate ethical, social, and legal issues through multi-method, sociotechnical, interpretive and ethnographic, and interactionist evaluation approaches. Such evaluation can help telehealth, and other information technologies, be integrated into healthcare ethically and effectively.

Int J Med Inform2020       LitCov and CORD-19
593Motivations for Social Distancing and App Use as Complementary Measures to Combat the COVID-19 Pandemic: Quantitative Survey Study  

BACKGROUND: The current COVID-19 pandemic is showing negative effects on human health as well as on social and economic life. It is a critical and challenging task to revive public life while minimizing the risk of infection. Reducing interactions between people by social distancing is an effective and prevalent measure to reduce the risk of infection and spread of the virus within a community. Current developments in several countries show that this measure can be technologically accompanied by mobile apps; meanwhile, privacy concerns are being intensively discussed. OBJECTIVE: The aim of this study was to examine central cognitive variables that may constitute people’s motivations for social distancing, using an app, and providing health-related data requested by two apps that differ in their direct utility for the individual user. The results may increase our understanding of people’s concerns and convictions, which can then be specifically addressed by public-oriented communication strategies and appropriate political decisions. METHODS: This study refers to the protection motivation theory, which is adaptable to both health-related and technology-related motivations. The concept of social trust was added. The quantitative survey included answers from 406 German-speaking participants who provided assessments of data security issues, trust components, and the processes of threat and coping appraisal related to the prevention of SARS-CoV-2 infection by social distancing. With respect to apps, one central focus was on the difference between a contact tracing app and a data donation app. RESULTS: Multiple regression analyses showed that the present model could explain 55% of the interindividual variance in the participants’ motivation for social distancing, 46% for using a contact tracing app, 42% for providing their own infection status to a contact tracing app, and 34% for using a data donation app. Several cognitive components of threat and coping appraisal were related to motivation measurements. Trust in other people’s social distancing behavior and general trust in official app providers also played important roles; however, the participants’ age and gender did not. Motivations for using and accepting a contact tracing app were higher than those for using and accepting a data donation app. CONCLUSIONS: This study revealed some important cognitive factors that constitute people’s motivation for social distancing and using apps to combat the COVID-19 pandemic. Concrete implications for future research, public-oriented communication strategies, and appropriate political decisions were identified and are discussed.

J Med Internet Res2020       LitCov and CORD-19
594COVID-19 in children and adolescents in Europe: a multinational, multicenter cohort study  

BACKGROUND: To date, few data on paediatric COVID-19 have been published, and most reports originate from China. This study aimed to capture key data on children and adolescents with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection across Europe to inform physicians and health-care service planning during the ongoing pandemic. METHODS: This multicentre cohort study involved 82 participating health-care institutions across 25 European countries, using a well established research network—the Paediatric Tuberculosis Network European Trials Group (ptbnet)—that mainly comprises paediatric infectious diseases specialists and paediatric pulmonologists. We included all individuals aged 18 years or younger with confirmed SARS-CoV-2 infection, detected at any anatomical site by RT-PCR, between April 1 and April 24, 2020, during the initial peak of the European COVID-19 pandemic. We explored factors associated with need for intensive care unit (ICU) admission and initiation of drug treatment for COVID-19 using univariable analysis, and applied multivariable logistic regression with backwards stepwise analysis to further explore those factors significantly associated with ICU admission. FINDINGS: 582 individuals with PCR-confirmed SARS-CoV-2 infection were included, with a median age of 5·0 years (IQR 0·5–12·0) and a sex ratio of 1·15 males per female. 145 (25%) had pre-existing medical conditions. 363 (62%) individuals were admitted to hospital. 48 (8%) individuals required ICU admission, 25 (4%) mechanical ventilation (median duration 7 days, IQR 2–11, range 1–34), 19 (3%) inotropic support, and one (<1%) extracorporeal membrane oxygenation. Significant risk factors for requiring ICU admission in multivariable analyses were being younger than 1 month (odds ratio 5·06, 95% CI 1·72–14·87; p=0·0035), male sex (2·12, 1·06–4·21; p=0·033), pre-existing medical conditions (3·27, 1·67–6·42; p=0·0015), and presence of lower respiratory tract infection signs or symptoms at presentation (10·46, 5·16–21·23; p<0·0001). The most frequently used drug with antiviral activity was hydroxychloroquine (40 [7%] patients), followed by remdesivir (17 [3%] patients), lopinavir–ritonavir (six [1%] patients), and oseltamivir (three [1%] patients). Immunomodulatory medication used included corticosteroids (22 [4%] patients), intravenous immunoglobulin (seven [1%] patients), tocilizumab (four [1%] patients), anakinra (three [1%] patients), and siltuximab (one [<1%] patient). Four children died (case-fatality rate 0·69%, 95% CI 0·20–1·82); at study end, the remaining 578 were alive and only 25 (4%) were still symptomatic or requiring respiratory support. INTERPRETATION: COVID-19 is generally a mild disease in children, including infants. However, a small proportion develop severe disease requiring ICU admission and prolonged ventilation, although fatal outcome is overall rare. The data also reflect the current uncertainties regarding specific treatment options, highlighting that additional data on antiviral and immunomodulatory drugs are urgently needed. FUNDING: ptbnet is supported by Deutsche Gesellschaft für Internationale Zusammenarbeit.

Lancet Child Adolesc Health2020       LitCov and CORD-19
595Monitoring the severe acute respiratory syndrome epidemic and assessing effectiveness of interventions in Hong Kong Special Administrative Region  

N/A

J Epidemiol Community Health2003       CORD-19
596Epidemiology of community-acquired respiratory tract infections in adults: Incidence, etiology and impact  

Abstract Upper respiratory tract infections are the most common types of infectious diseases among adults. It is estimated that each adult in the United States experiences two to four respiratory infections annually. The morbidity of these infections is measured by an estimated 75 million physician visits per year, almost 150 million days lost from work, and more than $10 billion In costs for medical care. Serotypes of the rhinoviruses account for 20 to 30 percent of episodes of the common cold. However, the specific causes of most upper respiratory infections are undefined. Pneumonia remains an important cause of morbidity and mortality for nonhospitalized adults despite the widespread use of effective antimicrobial agents. There are no accurate figures on the number of episodes of pneumonia that occur each year in ambulatory patients. In younger adults, the atypical pneumonia syndrome Is the most common clinical presentation; Mycoplasma pneumoniae is the most frequently Identified causative agent. Other less common agents include Legionelia pneumophila, influenza viruses, adenoviruses, and Chiamydia. More than half a million adults are hospitalized each year with pneumonia. Persons older than 65 years of age have the highest rate of pneumonia admissions, 11.5 per 1,000 population. Pneumonia ranks as the sixth leading cause of death in the United States. The pathogens responsible for community-acquired pneumonlas are changing. Forty years ago, Streptococcus pneumoniae accounted for the majority of infections. Today, a broad array of community-acquired pathogens have been implicated as etiologic agents Including Leglonella species, gram-negative bacilli, Hemophilus influenzae, Staphylococcus aureus and nonbacterial pathogens. Given the diversity of pathogenic agents, it has become imperative for clinicians to establish a specific etiologic diagnosis before initiating therapy or to consider the diagnostic possibilities and treat with antimicrobial agents that are effective against the most likely pathogens.

Am J Med1985       CORD-19
597CT Imaging Features of 2019 Novel Coronavirus (2019-nCoV)  

In this retrospective case series, chest CT scans of 21 symptomatic patients from China infected with the 2019 novel coronavirus (2019-nCoV) were reviewed, with emphasis on identifying and characterizing the most common findings. Typical CT findings included bilateral pulmonary parenchymal ground-glass and consolidative pulmonary opacities, sometimes with a rounded morphology and a peripheral lung distribution. Notably, lung cavitation, discrete pulmonary nodules, pleural effusions, and lymphadenopathy were absent. Follow-up imaging in a subset of patients during the study time window often demonstrated mild or moderate progression of disease, as manifested by increasing extent and density of lung opacities. © RSNA, 2020

Radiology2020       LitCov and CORD-19
598Clinical characteristics and risk factors of patients with severe COVID-19 in Jiangsu province, China: a retrospective multicenter cohort study  

BACKGROUND: Coronavirus Disease-2019 (COVID-19) pandemic has become a major health event that endangers people health throughout China and the world. Understanding the factors associated with COVID-19 disease severity could support the early identification of patients with high risk for disease progression, inform prevention and control activities, and potentially reduce mortality. This study aims to describe the characteristics of patients with COVID-19 and factors associated with severe or critically ill presentation in Jiangsu province, China. METHODS: Multicentre retrospective cohort study of all individuals with confirmed Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infections diagnosed at 24 COVID-19-designated hospitals in Jiangsu province between the 10th January and 15th March 2020. Demographic, clinical, laboratory, and radiological data were collected at hospital admission and data on disease severity were collected during follow-up. Patients were categorised as asymptomatic/mild/moderate, and severe/critically ill according to the worst level of COVID-19 recorded during hospitalisation. RESULTS: A total of 625 patients, 64 (10.2%) were severe/critically ill and 561 (89.8%) were asymptomatic/mild/moderate. All patients were discharged and no patients died. Patients with severe/critically ill COVID-19 were more likely to be older, to be single onset (i.e. not belong to a cluster of cases in a family/community, etc.), to have a medical history of hypertension and diabetes; had higher temperature, faster respiratory rates, lower peripheral capillary oxygen saturation (SpO(2)), and higher computer tomography (CT) image quadrant scores and pulmonary opacity percentage; had increased C-reactive protein, fibrinogen, and D-dimer on admission; and had lower white blood cells, lymphocyte, and platelet counts and albumin on admission than asymptomatic/mild/moderate cases. Multivariable regression showed that odds of being a severe/critically ill case were associated with age (year) (OR 1.06, 95%CI 1.03–1.09), lymphocyte count (10(9)/L) (OR 0.25, 95%CI 0.08–0.74), and pulmonary opacity in CT (per 5%) on admission (OR 1.31, 95%CI 1.15–1.51). CONCLUSIONS: Severe or critically ill patients with COVID-19 is about one-tenths of patients in Jiangsu. Age, lymphocyte count, and pulmonary opacity in CT on admission were associated with risk of severe or critically ill COVID-19.

BMC Infect Dis2020       LitCov and CORD-19
599Time Course of Lung Changes at Chest CT during Recovery from COVID-19  

BACKGROUND: Chest CT is used to assess the severity of lung involvement in COVID-19 pneumonia. PURPOSE: To determine the change in chest CT findings associated with COVID-19 pneumonia from initial diagnosis until patient recovery. MATERIALS AND METHODS: This retrospective review included patients with RT-PCR confirmed COVID-19 infection presenting between 12 January 2020 to 6 February 2020. Patients with severe respiratory distress and/ or oxygen requirement at any time during the disease course were excluded. Repeat Chest CT was obtained at approximately 4 day intervals. The total CT score was the sum of lung involvement (5 lobes, score 1-5 for each lobe, range, 0 none, 25 maximum) was determined. RESULTS: Twenty one patients (6 males and 15 females, age 25-63 years) with confirmed COVID-19 pneumonia were evaluated. These patients under went a total of 82 pulmonary CT scans with a mean interval of 4±1 days (range: 1-8 days). All patients were discharged after a mean hospitalized period of 17±4 days (range: 11-26 days). Maximum lung involved peaked at approximately 10 days (with the calculated total CT score of 6) from the onset of initial symptoms (R2=0.25), p<0.001). Based on quartiles of patients from day 0 to day 26 involvement, 4 stages of lung CT were defined: Stage 1 (0-4 days): ground glass opacities (GGO) in 18/24 (75%) patients with the total CT score of 2±2; (2)Stage-2 (5-8d days): increased crazy-paving pattern 9/17 patients (53%) with a increase in total CT score (6±4, p=0.002); (3) Stage-3 (9-13days): consolidation 19/21 (91%) patients with the peak of total CT score (7±4); (4) Stage-4 (≥14 days): gradual resolution of consolidation 15/20 (75%) patients with a decreased total CT score (6±4) without crazy-paving pattern. CONCLUSION: In patients recovering from COVID-19 pneumonia (without severe respiratory distress during the disease course), lung abnormalities on chest CT showed greatest severity approximately 10 days after initial onset of symptoms.

Radiology2020       LitCov and CORD-19
600Association of Age With Likelihood of Developing Symptoms and Critical Disease Among Close Contacts Exposed to Patients With Confirmed SARS-CoV-2 Infection in Italy  

We quantified the probability of developing symptoms (respiratory or fever geq 37.5 {deg}C) and critical disease (requiring intensive care or resulting in death) of SARS-CoV-2 positive subjects. 5,484 contacts of SARS-CoV-2 index cases detected in Lombardy, Italy were analyzed, and positive subjects were ascertained via nasal swabs and serological assays. 73.9% of all infected individuals aged less than 60 years did not develop symptoms (95% confidence interval: 71.8-75.9%). The risk of symptoms increased with age. 6.6% of infected subjects older than 60 years had critical disease, with males at significantly higher risk.

JAMA Netw Open2021       LitCov and CORD-19

(1) COVID-19 Open Research Dataset (CORD-19). 2020. Version 2022-06-02. Retrieved from https://ai2-semanticscholar-cord-19.s3-us-west-2.amazonaws.com/historical_releases.html. Accessed 2022-06-05. doi:10.5281/zenodo.3715506
(2) Chen Q, Allot A, & Lu Z. (2020) Keep up with the latest coronavirus research, Nature 579:193 and Chen Q, Allot A, Lu Z. LitCovid: an open database of COVID-19 literature. Nucleic Acids Research. 2020. (version 2023-01-10)
(3) Currently tweets of June 23rd to June 29th 2022 have been considered.

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